Sex Differences In The Brain: A Tale Of Two Membranes
Sex differencesin the brain:a tale of two membranesJennifer SwannDepartment of Biological SciencesLehigh UniversityBethlehem, PA, USA
Mating strategiesAsexual Everyone is the same sex Advantage - you do not need to find a mate Disadvantage - everyone is the sameSexual Two (or more) sexes Advantage - genetic recombination Disadvantage - more difficult to find a partner
Asexual reproduction Budding : offspring develop as a growth onthe body of the parent jellyfishes , echinoderms, corals, tapeworms Parthenogenesis- egg develops withoutfertilization Some fishes, several kinds of insects, and a fewspecies of lizards. Cloning-artifcial reproducution of animalsfrom non germ cells Mice, sheep, cats, donkey
Disadvantage:
Mating strategiesAsexual Everyone is the same sex Advantage - you do not need to find a mate Disadvantage - everyone is the sameSexual Two (or more) sexes Advantage - genetic recombination Disadvantage - more difficult to find a partner
Two sexes - How different?A wee quiz How many sex differences can youname in 5 minutes?
Two different sexes - how different? Phenotype- differences obvious to the eye Physiology-the way the body works Behavior - actions Genotype- genetic differences
Phenotypes- how do males and females lookdifferent?
Physiology: Differences critical to medicineHeart Disease -Heart disease kills 500,000 American women each year-over 50,000more women than men.Depression -Women are 2-3 times more likely than men to suffer fromdepression.Lung Cancer -Women are more likely to develop lung cancer than men.STDs -Women are 2 times more likely than men to contract a sexuallytransmitted disease, and 10 times more likely to contract HIV.Anesthesia -Women tend to wake up from anesthesia more quickly than men.Autoimmune Disease - 3 times as many women as men suffer from autoimmunediseases, such as multiple sclerosis, rheumatoid arthritis, and lupus.Alcohol -After consuming the same amount of alcohol, women have higherblood alcohol content than men-even allowing for size differences.Pain -Pain medications are far more effective in relieving pain in womenthan in men.http://www.womens-health.org/
Behaviors: do men and women behavedifferently?Verbal memory- women excel at tasks involving memory of word lists. Recentstudies suggest that verbal memory is stored bilaterally in femalesand unilaterally in malesSpatial memory- male rats and humans are much better at navigating space andremembering spatial details than femalesAggression- males of most species are more aggressive in defending territorywhile females excel at parental aggressionParenting-species specific differences. In some species only the female parents.In others both parents share the role equally. In others only themale parents.Copulation- highly dimorphic in both preference and motor patterns. In mostspecies the majority of males prefer females and females prefermales. In mammals male copulatory behavior utilizes the ventralmuscles while female copulatory behavior utilizes the dorsalmusculature
What causes these differences?The true story ofJ O H N /J O A NBy John ColapintoThe Rolling Stone, December 11,1997. Pages 54-97After suffering the complete lossof his penis to a botchedcircumcision when he was 8months old a sex-changeoperation was performed thatinvolved clinical castration,genital surgery and a 12-yearprogram of social, mental andhormonal conditioning.Environment ?
Or Genotype?Men and women aresimilar in geneticmake up except for1 chromosome .Professor Victor AxiakForget The Budget! - WHAT ABOUT SEX?Dossier Science 27 November N.asp?id 6918&po 2
The X and Y chromosome Women have 2 X Men have X and Y Men and women differby about 10% of theirgenetic make up
Genes regulate hormones:hormones regulate differentiationXYtestisXXovary
Testing the hypothesis Fetus testosterone male Then female testosterone male sexbehavior
What regulates behavior? The Brain! If the brain regulates behavior andbehavior is sexually dimorphic then thebrain must be sexually dimorphic
Sex differences in the size of neural areas have beencorrelated with sex differences in behavior The sexuallydimorphicpreoptic nucleusis larger in themale than thefemale.
Perinatal manipulation of hormonesinduces differences in the brain Sex differences in the SDN areeliminated in females treated withtestosterone at birth The role of the SDN in behaviorhas not been determined!
The hamster - a model system Hamsters depend onchemosensory signalsfor social interactions Researchers have usedthis finding to map thepathways that controlsocial behavior
Pheromones are detected by two chemosensorysystems
Chemosensorysignals(pheromones) arerelayed from theolfactory bulbs tothe BNST andamygdalaand the MPOAby a ePACo
What about the preoptic area? Lesions of the preoptic area eliminatemating in all vertebrate speciesexamined to date What about the hamster?
The MPN magLesions of this nucleus eliminate matingbehavior in the male hamsterccCPfstplGPMPN magaMPNoxb
No stimulusExposure tofemalepheromonesstimulatesneurons in theolfactory bulbs,Me, BNST andMPN magof males .PheromonesOlfactorybulbsMeBNSTMPN mag
No stimulusPheromonesalso stimulatethe BST andMePheromonesMeBNSTBut not theMPN magof females!MPN mag
MOBExposure tofemalepheromonesstimulates thechemosensorypathway in asex specific wayAOBPIAOBAOB
SynapsesThe connection between 2neurons: The axon of one neuronstimulates the dendrites ofanother The axon is presynaptic The dendrite is post synaptic
PresynapticSex differences in the density of synaptophysin
PresynapticSex differences in cluster size
Interpretation Testosterone has sex dependent and independent effecs Testosterone regulates the number of synapses in males but not infemales Testoterone regulates the size of synapses in both sexes
Injections of BDA labelterminals the MPNmag
Testosteroneregulates boutonnumberSex determineshow much
Testosterone regulates of en passant bouton size inmales but not females
Testosterone regulates end bouton size in both sexes
Post synaptic: what about the dendrites?The Golgi stain
Spines
Testosterone regulates dendrites in the MPOASpines per 10µmSpine Density MPOASpine Density LPOA66554433221100Intact MaleCastrated MaleGroupCastrate TIntact MaleCastrated MaleC T
model
MechanismPost synaptic
Antisense DNA oligonucleotides can beused to block translation of mRNAhttp://en.wikipedia.org/wiki/File:Antisense DNA oligonucleotide.pn
Antisense PSD-95 will prevent newsynthesis of PSD-95 proteinSite-specific injection ofAntisense PSD-95Into the MPOAShould mimic a lack of nNOSfunction in the MPOA, andlead to a lack of responding ininjected animals
Antisense PSD-95Needle track reconstructionWestern Blot for the presence of PSD-95
One day following antisense PSD-95 or sham injectionMounts10% of spentinvestigating30Number ofejaculations14Number of 2500ShamAS PSD-95Sham AS PSD-950ShamAS PSD-9550% of shams showed sex behaviors while none of the ASanimals 50sham0sham AS PSD-95Investigation% of time 30252015105035Number ofEjaculationsNumber of MountsThree weeks following injectionMountsAS PSD95sham AS PSD95
Mechanism presynapticAndrogenreceptors interminals!
What have we learned? Testosterone regulates neuronal morphology and functionin a sex specific manner Changes to synaptic density may underlie changes inbehavior PSD 95 in the MPOA is essential for male hamster matingbehavior
Heart Disease - Heart disease kills 500,000 American women each year-over 50,000 more women than men. Depression - Women are 2-3 times more likely than men to suffer from depression. Lung Cancer - Women are more likely to develop lung cancer than men. STDs - Women
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